Basic and applied biological research and biotechnology are limited by the ability to get information into and from living systems and to act on information inside living systems. For example, there are only a small number of inducible promoter systems available to provide control over gene expression in response to exogenous molecules. Many of the molecular inputs to these systems are not ideal for broad implementation, because they can be expensive and introduce undesired pleiotropic effects. In addition, broadly applicable methods for getting information from cells noninvasively have been limited to strategies that rely on protein and promoter fusions to fluorescent proteins, which enable researchers to monitor protein levels and localization and transcriptional outputs of networks, leaving a significant amount of the cellular information content currently inaccessible.
A striking example of a biological communication and control system is the class of RNA-regulatory elements called riboswitches, comprising distinct sensor and actuation (gene-regulatory) functions, that control gene expression in response to specific ligand concentrations. Building on these natural examples, engineered riboswitch elements have been developed for use as synthetic ligand-controlled gene-regulatory systems. However, research to date has largely focused on the generation of specific instances of RNA devices, which do not necessarily guide researchers in how to translate that particular instance into other instances useful for specific systems or applications. Often times, the activity of these RNA devices is dependent on the particular system in which it was developed, including sequences immediately surrounding the regulator element, and modularity is not maintained.
As a result, these early examples of switch engineering do not address the challenges posed above, because they lack portability across organisms and systems, and their designs and construction do not support modularity and component reuse.